Low-Nicotine Cigarettes Studied As A Smoking Cessation Tool

Rose will present his findings in poster presentations at the annual meeting of the Society for Research on Nicotine and Tobacco in Savannah, Ga., Feb. 20-23. The two separate studies focus on the use of two different denicotinized cigarettes, those cigarettes with extremely low levels of nicotine often referred to as "de-nics," as a device for weaning smokers off of all cigarettes.

A third study Rose will present at the meeting revisits his previous work that explores the possibility of using the drug mecamylamine in smoking cessation programs. That study suggests that the drug – once used as an anti-hypertensive – might find use in helping women stop smoking.

One study used Omni, the Vector Tobacco Inc. cigarette that delivers 0.02 milligrams of nicotine; and the second used Next, a low-nicotine cigarette test-marketed by Philip Morris in the early 1990s.

"Our studies show that denicotinized cigarettes can be an effective method of reducing nicotine dependence for some people. Our goal is permanent smoking cessation of every kind of cigarette and if there is a cigarette that shows promise in this area, I think it's worth exploring further," Rose said.

Nicotine is an addictive chemical in tobacco. Low-nicotine cigarettes, or the "de-nics," generally deliver less than 0.1 milligram of nicotine, compared with 1 to 2 milligrams of nicotine in full-flavored brands.

The study involving Omni cigarettes was supported by an unrestricted financial gift from Vector. Rose does not have a financial interest in Vector. The study using Next cigarettes was funded by the National Institute on Drug Abuse (NIDA). Rose's past research has been supported by grants from the National Institutes of Health. He is most known for his role in developing the nicotine patch.

In the first study reported, the scientists showed that the amount of smoke inhaled can be enough to satisfy the craving for cigarettes, even in the near absence of nicotine. Past research had shown when nicotine levels in cigarettes are reduced, smokers tend to overcompensate for the lack of nicotine by smoking more cigarettes or by taking longer drags. In the study on Vector's de-nic cigarettes, Rose and his colleagues compared the smoking behavior and blood nicotine levels of 16 smokers who, during one eight-hour period, smoked low-tar/low-nicotine cigarettes with ventilated filters. In a second, eight-hour session, the same group of smokers smoked the high-tar/low-nicotine cigarettes.

The scientists found that participants smoked 60 percent more of the low-tar/low-nicotine cigarettes than the high-tar variety with nearly no nicotine. Subjects smoked the de-nic cigarettes with the same intensity as their usual brands, based on measurements of carbon monoxide levels.

Rose said his finding suggests that the amount of smoke a smoker inhales can satisfy the craving to smoke despite the absence of nicotine. "These results suggest that delivery of substantial amounts of smoke with selective reductions in nicotine, deters compensatory smoking behavior," he said. In the second study, using the de-nic Next cigarettes, 16 smokers were tested to examine which was more important to the smoker: the ritual of lighting up or the need to satisfy nicotine cravings.

In seven sessions, smokers were asked to smoke their regular brand of cigarettes, but in other sessions they were also asked to inhale a specified amount of smoke, either from their usual brands of cigarettes or from Next. During other sessions subjects received intravenous (i.v.) infusions of nicotine, administered either at a slow continuous rate or as rapid infusions. The effects of i.v. nicotine were assessed by comparing it to an inactive saline infusion.

Rose and his colleagues found that the nicotine i.v. infusions did not significantly discourage smokers from smoking their usual brands of cigarettes. Subjects smoked only about 15 percent less when receiving nicotine infusions alone. However, smokers who smoked the de-nic cigarettes reduced their smoke intake by about 40 percent, even without receiving i.v. nicotine.

The i.v. nicotine infusions did little to relieve the craving to smoke, although the rapid infusion of nicotine did have a slight effect on craving. Other symptoms, such as irritability, were effectively relieved by nicotine, regardless of how quickly the nicotine i.v. solutions were administered.

"These results suggest that regulation of smoke intake seems to be strongly linked to the sensory and habit components," said Rose. "Some symptoms, such as irritability, seem to be relieved effectively by nicotine, but other symptoms, like craving, are not. Even though they received nicotine in an i.v., the smokers still wanted to smoke. And those who smoked the denicotinized cigarettes without receiving nicotine in an i.v. were more satisfied than those deprived of all cigarettes.

"These findings suggest that comprehensive smoking cessation treatment programs need to use different techniques to address both the craving for nicotine and the habit of smoking," Rose said. In the third research effort Rose discussed at the meeting, he reviewed previously reported studies in which the drug mecamylamine was used in conjunction with the nicotine patch in smoking cessation therapy.

The combination has not proven to be overwhelmingly successful in men and women, said Rose. However, studies he and his colleagues conducted on the use of mecamylamine with the nicotine patch, suggest that the drug might be better suited for women who are trying to quit smoking.

In his poster presentation for the SRNT conference, Rose combined data from three randomized, double-blind, placebo-controlled studies in which 291 subjects were treated with mecamylamine.

The scientists' analysis showed that 44.2 percent of women abstained from smoking for at least four weeks with the aid of mecamylamine and the nicotine patch. This compared to 15.6 percent for women who did not receive mecamylamine. For the men, the rates were 40.2 percent abstinence with mecamylamine and the nicotine patch, compared to 35 percent without mecamylamine.

"There are important gender differences in tobacco addiction, which we are just beginning to unravel and understand. There are a number of theories about why mecamylamine is more effective in women," Rose said.

One theory is that women value more the sensory cues of smoking, such as taste. Mecamylamine may work by breaking the learned association between these sensory cues and nicotine reward. Another theory is that the hormone progesterone also blocks nicotinic receptors, so women already have a natural nicotinic receptor antagonist which might complement the effects of mecamylamine, Rose said.

"These are just speculations. We really don't have an answer, but women tend to respond better to mecamylamine treatment compared to men," he said.

The mecamylamine/nicotine patch studies were funded by the National Institute on Drug Abuse and the Medical Research Service of the U.S. Department of Veterans Affairs.